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Topical Area: Obesity

Obesity (Poster Session)

(P31-021-23) Effect of Obesity and Metformin on Serum Metabolic Changes in Lean and Obese Zucker Rats

Monday, July 24, 2023
12:45 PM – 1:45 PM ET
Location: Poster Board 243

    Presenting Author(s)

  • Reza Hakkak, PhD

    Professor
    University of Arkansas for Medical Sciences
    Little Rock, Arkansas, United States

    • Co-Author(s)

  • SM

    Stepan Melnyk, MD, Ph.D.

    Arkansas Children`s Research Institute
    Little Rock, Arkansas, United States

Disclosure(s):
Reza Hakkak, PhD: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: Utilizing of untargeted metabolomics analysis to assess metabolic consequences of metformin treatment in lean and obese Zucker rat model.

Methods: 28 five-week-old female lean and obese (fa/fa) Zucker rats fed semi-purified AIN-93G diet for 8 weeks and then all rats were randomly assigned to: (6 rats/group): 1) lean control (LC), 2) obese control (OC) 3) lean with metformin (LM) and 4) obese metformin (OM); for 10 weeks. Metformin was mixed with AIN-93G diet at 1,000 mg/kg of diet and rats were euthanized and plasma were collected for Untargeted Metabolomics Analysis (UTMA). Samples preparation procedure included deproteinization of plasma and purification of extract. We utilized combination of HPLC-ECD, HPLC-UV and LC-MS platforms to collect data. HPLC-ECD was used separately from combined HPLC-UV and LC-MS platforms. 

Results: Using UTMA analysis produced more than 400 measurable peaks. The top 50 highest and good chromatographic quality corresponding peaks were selected.  All 50 peaks had individual numerical name (or ID) based on their retention time and peaks ID sequence was identical for all 4 groups of animals.  In lean animal peak height of 16 (32%) metabolites of LC rats were significantly (P < 0.05) higher compared to LM rats and only 3 (6%) peaks were significantly (P < 0.05) higher in LM rats compare LC rats, followed 23 (46%) peaks no differences and 8 (16%) peaks on the border line (0.1 >P >0.05). In obese animal peak height of 13 (26%) metabolites of OM rats were significantly (P < 0.05) higher compared to OC rats and only 6 (12%) peaks were significantly (P < 0.05) higher in OC rats compare to OM rats followed 16 (32%) peaks no differences and 15 (30%) peaks on the border line (0.1 >P >0.05). In lean and obese animal treated with metformin, pick height of 19 (38%) metabolites were significantly (P < 0.05) higher in LM rats compared to OM and almost equal 18 (36%) peaks were significantly (P < 0.05) higher in OM rats compare to LM rats, followed 7 (14%) peaks no differences and 6 (12%) on the border line (0.1 >P >0.05).

Conclusions: These data showed that obesity and metformin treatment of the Zucker rats can significantly modify a profile of systemic metabolic status. This finding will contribute for improving of future experiments design and data analysis with this rat model.

Funding Sources: Arkansas Biosciences Institute